Results from a preliminary study indicate that among patients with relapsing-remitting multiple sclerosis, treatment with nonmyeloablative hematopoietic stem cell transplantation (low intensity stem cell transplantation) was associated with improvement in measures of disability and quality of life, according to a study in the Journal of the American Medical Association.

Fifty per cent of patients with multiple sclerosis are unable to continue employment after 10 years of diagnosis or are unable to walk after 25 years. Despite an annual cost of approximately US$47,000 per patient to treat multiple sclerosis, no therapy approved by the US Food and Drug Administration (FDA) has been shown to significantly reverse neurological disability or improve quality of life.

Multiple sclerosis is thought to be an immune­mediated disorder of the central nervous system. Autologous haematopoietic stem cell transplantation (HSCT) is a form of immune suppression, which unlike standard immune-based drugs, is designed to reset rather than suppress the immune system. Richard K Burt of the Northwestern University Feinberg School of Medicine, Chicago, USA, and colleagues studied the association of nonmyeloablative HSCT with neurological disability and other clinical outcomes in patients with relapsing-remitting multiple sclerosis (defined as acute relapses followed by partial or complete recovery and stable clinical manifestations between relapses; n=123) or secondary-progressive multiple sclerosis (defined as a gradual progression of disability with or without superimposed relapses; n=28) treated between 2003 and 2014.

Outcome analysis was available for 145 patients with an average follow-up of 2.5 years. On the Expanded Disability Status Scale (EDSS) score, there was significant improvement in 41 patients (50% of patients tested at two years) and in 23 patients (64% of patients tested at four years). “To our knowledge, this is the first report of significant and sustained improvement in the EDSS score following any treatment for multiple sclerosis,” the authors write.

Receipt of HSCT was also associated with improvement in physical function, cognitive function and quality of life. There was also a reduction in the volume of brain lesions associated with multiple sclerosis seen on MRI images. Four-year relapse-free survival was 80% and progression-free survival was 87%.

Patient selection is important in determining outcome, the researchers write. “In the post hoc analysis, the EDSS score did not improve in patients with secondary-progressive multiple sclerosis or in those with disease duration longer than 10 years.”

The authors note the results are limited because this was an observational study without a control group. “Definitive conclusions will require a randomised trial; however, this analysis provides the rationale, appropriate patient selection, and therapeutic approach for a randomised study.”

Stephen L Hauser, University of California, San Francisco, USA, writes that the study by Burt et al, taken together with other available evidence, enables several conclusions to be made with reasonable confidence. “First, autologous HSCT does not appear to be effective against established progressive forms of the condition and, absent new data, additional trials of these protocols are probably not indicated for patients with progressive multiple sclerosis. Second, immunosuppressive regimens that include HSCT appear to be effective against the relapsing-remitting form of multiple sclerosis, at least over several years of observation. However, it is by no means clear that the beneficial effects result from the infusion of stem cells rather than from the conditioning regimen. Given the availability of highly effective FDA-approved therapies against relapsing-remitting multiple sclerosis, it would seem reasonable to use these proven monotherapies in the clinical setting before considering complex HSCT regimens.”

Hauser continues, “Third, the mechanism of action of autologous HSCT in MS needs to be clarified. Fourth, it is important to remember that multiple sclerosis is a chronic disease, usually arising in young adults and lasting throughout the lifespan. Many important disability-related outcomes take many years or decades to develop. To understand the role of any therapy, and especially an intensive regimen with uncertain long-term risk, very long follow-up periods are required to meaningfully assess if the disease has indeed been rebooted over the long term, and also to increase confidence that these therapies have not caused undue harm.”